Here we propose to design a Nanomedicine Center for Molecular Membrane Physiology. This Center will develop and apply nanoscience tools to study and manipulate the protein and lipid nanomachines that precisely regulate the flow of information and material between the cell and its environment. Defects in these nanomachines are responsible for a host of diseases including cystic fibrosis, diabetes, and cardiovascular disease. In addition, membrane proteins are the targets of about 2/3 of clinically relevant drugs and thus represent a tremendous opportunity for therapeutic intervention. The principle reasons for suggesting Molecular Membrane Physiology as a Center theme are that problems in this area are interrelated and a number of powerful nanoscale techniques are uniquely suited to study cellular nanomachinery in a membrane environment. We propose that the Center focus on developing and applying nanoscience tools to understand and manipulate: 1) vesicular transport, exocytosis and endocytosis, 2) the gating of ion channels, and 3) membrane receptor-mediated signaling. The Specific Aim of this proposal is to create a Concept Development Plan for the Nanomedicine Center. This process will be directed by "facilitators" who are nanotechnology-savvy experts in the 3 subthemes who will help focus discussions on the major problems of their field. They will assemble a Panel of Scientific and Technical Experts and lead discussions at a Membrane Nanomediciene Workshop to be held in December, 2004. Emerging nanoscience technology applicabe to questions in the 3 subthemes will be brought forward. Workshop participants will prioritize promising nanoscience approaches according to their potential impact on membrane nanomedicine. The Panel will also make recommendations for the organization of both the specific Membrane Nanomedicine Center and the entire NIH Nanomedicine Center Initiative with input provided from a survey of nationally prominent Center directors and Center Investigators.